Relationship between PD-L1 expression and prognostic factors in high-risk cutaneous squamous and basal cell carcinoma.
This study aimed to investigate the programmed cell death-ligand 1 (PD-L1) expression in cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) and its relationship with prognostic factors in tumors that are not in the head and neck region and are therefore relatively less exposed to the sun. This retrospective cross-sectional study included 25 invasive cSCC and 42 BCC cases with a diameter ≥ 2 cm located outside the head and neck region from 2010 to 2018. The biopsy samples were examined based on the membranous PD-L1 (22C3 clone) staining. Staining results were scored as follows: 0, no staining (negative); 1, < 10% PD-L1 positivity of tumor cells; and 2, ≥ 10% PD-L1 positivity of tumor cells. PD-L1 positivity was not seen in any BCC cases, whereas 11 (44%) of cSCC cases were PD-L1 positive. No significant relationship was observed between PD-L1 expression and prognostic parameters, including tumor diameter, tumor depth, and lymphovascular or perineural invasion in the cSCC group. PD-L1 expression was not associated with prognostic factors in the early stages of BCC and SCC located outside the head and neck region. Therefore, investigating the PD-L1 expression seems to be more relevant in patients with advanced-stage disease.


Repeat migration and remittances as mechanisms for wealth inequality in 119 communities from the Mexican Migration Project data.
To evaluate the distributional impact of remittances in origin communities, prior research studied how migrants' selectivity by wealth varies with migration prevalence in the community or prior migration experience of the individual. This study considers both patterns; it examines selectivity separately in low- and high-prevalence communities and for first-time and repeat migrants. Based on data from 18,042 household heads in 119 Mexican communities from the Mexican Migration Project, the analyses show that (1) first-time migrants in low-prevalence communities come from poor households, whereas repeat migrants in high-prevalence communities belong to wealthy households; and (2) higher amounts of remittances reach wealthy households. These results suggest that repeat migration and remittances may be mechanisms for wealth accumulation in the study communities. Descriptive analyses associate these mechanisms with increasing wealth disparities between households with and without migrants, especially in high-prevalence communities. The study, similar to prior findings, shows the importance of repeat migration trips, which, given sustained remittances, may amplify the wealth gap between migrants and nonmigrants in migrant-sending communities. The study also qualifies prior findings by differentiating between low- and high-prevalence communities and observing a growing wealth gap only in the latter.


Amphiphilic surface chemistry of fullerenols is necessary for inhibiting the amyloid aggregation of alpha-synuclein NACore.
Featuring small sizes, caged structures, low cytotoxicity and the capability to cross biological barriers, fullerene hydroxy derivatives named fullerenols have been explored as nanomedicinal candidates for amyloid inhibition. Understanding the surface chemistry effect of hydroxylation extents and the corresponding amyloid inhibition mechanisms is necessary for enabling applications of fullerenols and also future designs of nanomedicines in mitigating amyloid aggregation. Here, we investigated effects of C60(OH)n with n = 0-40 on the aggregation of NACore (the amyloidogenic core region of the non-amyloid-β component in α-synuclein), the amyloidogenic core of α-synuclein, by computational simulations, transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, thioflavin-T (ThT) fluorescence kinetics and viability assays. Computationally, NACore assembled into cross-β aggregates via intermediates including β-barrels, which are postulated as toxic oligomers of amyloid aggregation. Hydrophobic C60 preferred to self-assemble, and NACore bound to the surface of C60 nano-clusters formed β-sheet rich aggregates - i.e., having little inhibition effect. Amphiphilic C60(OH)n with n = 4-20 displayed significant inhibition effects on NACore aggregation, where hydrogen bonding between hydroxyls and peptide backbones interrupted the formation of β-sheets between peptides adsorbed onto the surfaces of fullerenols or fullerenol nano-assemblies due to hydrophobic interactions. Thus, both cross-β aggregates and β-barrel intermediates were significantly suppressed. With hydroxyls increased to 40, fullerenols became highly hydrophilic with reduced peptide binding and thus an inhibition effect on amyloid aggregation. ThT, FTIR and TEM characterization of C60(OH)n with n = 0, 24, & 40 confirmed the computational predictions. Our results and others underscore the importance of amphiphilic surface chemistry and the capability of polar groups in forming hydrogen bonds with peptide backbones to render amyloid inhibition, offering a new insight for de-novo design of anti-amyloid inhibitors.


Timing of sexual debut and initiation of postsecondary education by early adulthood.
Although sexual debut has been negatively associated with adolescent educational performance and aspirations, it is not clear whether such relationships continue beyond adolescence. Initiation of postsecondary education by young adulthood was assessed among 3,965 participants in the National Longitudinal Study of Adolescent Health who had not experienced sexual intercourse at baseline. Associations between age at sexual debut and educational progress were examined in bivariate and multivariable Poisson regression analyses. Most respondents experienced sexual debut during adolescence: 15% before age 16 (early) and 53% at ages 16-18 (typical). Sixty-five percent of respondents initiated postsecondary education by early adulthood; however, the proportion was significantly lower among those who had had an early (49%) or typical sexual debut (63%) than among those who debuted late (78%). In unadjusted analyses, early and typical debut were associated with a reduced likelihood of initiation of postsecondary education for both females (relative risk ratios, 0.6 and 0.8, respectively) and males (0.7 and 0.8). However, in adjusted analyses, the associations were attenuated for females (0.8 and 0.9) and were at best marginally significant for males. Childbearing was a significant mediator of this relationship. Adolescent sexual debut appears to be modestly negatively associated with early adult postsecondary education initiation, particularly for females. Targeting mediators of the sexual debut-education relationship, such as early childbearing, could lead to effective interventions.


Numb regulates stability and localization of the mitotic kinase PLK1 and is required for transit through mitosis.
Numb functions in progenitor cell fate determination and early development, but it is also expressed in postdevelopmental tissues and cancers where its role is unclear. In this study, we report that a targeted knockdown of Numb expression causes a G(2)-M arrest and reduced cell growth in human melanoma cells. Co-immunoprecipitation and colocalization studies showed that Numb interacts with the serine/threonine polo-like kinase Plk1 and Numb cycles in a cell-cycle-dependent fashion along with this mitotic regulator. Interestingly, Numb expression was required for Plk1 protein stability and localization to the spindle poles during mitosis. Reduction in Numb expression resulted in mislocalization of Plk1 at both metaphase and anaphase, leading to disorganized γ-tubulin recruitment in centrosomes. Together, our findings present a novel function for Numb during symmetric cell division. We suggest that dysregulation of Numb expression results in mislocalized Plk1 and poor centrosomal γ-tubulin recruitment, potentially contributing to mitotic errors, aneuploidy, and cancer development.


Morphometric and simulation analyses of right hepatic vein reconstruction in adult living donor liver transplantation using right lobe grafts.
The incidence of clinically significant right hepatic vein (RHV) stenosis after adult living donor liver transplantation has been higher than expected. In this study, an assessment of the risk factors for the development of RHV stenosis in this context was undertaken. Hepatic anatomy, surgical techniques, and the incidence of RHV stenosis 1 year after transplantation were evaluated retrospectively in 225 recipients of right lobe grafts. These patients underwent independent RHV reconstruction, which was facilitated by the application of computed tomography morphometry and computational simulation analyses. Three types of preparation of the orifice of the graft RHV and 7 types of preparation for venoplasty of the recipient RHV were used. The frequency of high, middle, and low sites of RHV insertion into the inferior vena cava (IVC) was 56.0%, 36.4%, and 7.6%, respectively, for donors, and 26.7%, 58.7%, and 14.7%, respectively, for recipients. Nine patients (4%) developed RHV stenosis of early onset that required stent insertion during the first 2 postoperative weeks; in 12 patients (5.3%), RHV stenosis of delayed onset occurred. Inappropriate matching of RHV sites of insertion correlated with the incidence of stenosis of early onset (P = 0.039). Technical refinements to avoid adverse consequences of inappropriate ventrodorsal matching of RHV sites of insertion include making the recipient RHV orifice wide and enlarging the recipient IVC by a customized incision and patch venoplasty after anatomical assessment of the RHV and IVC of the graft and recipient.


To do or not to do: desirability and consistency mediate judgements of regret.
In 4 studies, the authors demonstrated that when errors associated with action were inconsistent with decision nakers' orientation, they were undesirable and produced more regret than did errors associated with inaction. Conversely, when errors associated with action were consistent with decision makers' orientation. they were desirable and produced less regret than did errors associated with inaction. Desirability and consistency mediated this relationship, independent of mutability. These results were obtained when judgments and decisions to act or not act were made in close temporal proximity to one another as well as when participants reflected on their past decisions. The authors provide an analysis of when counterfactuals would and would not be expected to mediate judgments of normality and regret.


Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer.
To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL.


The Cost of Being Cool: How Adolescent Pseudomature Behavior Maps onto Adult Adjustment.
During adolescence, one's status among peers is a major concern. Such status is often largely a function of popularity and establishing oneself as "cool." While there are conventional avenues to achieving status among adolescents, engaging in adult-like, or pseudomature, behaviors such as substance use or sexual activity is a frequent occurrence. Although past research has examined the consequences of adolescent delinquency, what remains unclear is the long-term fate of adolescents who are both popular and antisocial. Using data from a sample of African American males (N = 339) we employ latent class analysis to examine the adult consequences of achieving popularity during adolescence by engaging in pseudomature behavior. Our results identified four classes of adolescents: the conventionals, the pseudomatures, the delinquents, and the detached. The conventionals were low on popularity, pseudomature behavior, and affiliation with deviant peers but high on academic commitment. The pseudomatures were high on popularity, adult-like behavior, and academic commitment but low on affiliation with delinquent peers. The delinquents were low on popularity and school achievement but high on pseudomature behavior and affiliations with delinquent peers. Finally, the detached were low on school commitment, popularity and pseudomature behavior but they report high involvement with a delinquent peer group. By early adulthood, the costs of adolescent adult-like behavior were evident. Early popularity and academic commitment did not portend later social competence or college completion for the pseudomatures. Instead, they frequently experienced an early transition to parenthood, a likely consequence of precocious sexual activity. These findings suggest that interventions should not focus only on the most delinquent adolescents but also need to attend to the pseudomature students who are brimming with promise but are flirting with behaviors that may subvert realization of this potential.


Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2022.3.
Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2). Updates are published regularly and can be found at https://ascopubs.org/nsclc-non-da-living-guideline.


A New Integrated Approach to Taxonomy: The Fusion of Molecular and Morphological Systematics with Type Material in Benthic Foraminifera.
A robust and consistent taxonomy underpins the use of fossil material in palaeoenvironmental research and long-term assessment of biodiversity. This study presents a new integrated taxonomic protocol for benthic foraminifera by unequivocally reconciling the traditional taxonomic name to a specific genetic type. To implement this protocol, a fragment of the small subunit ribosomal RNA (SSU rRNA) gene is used in combination with 16 quantitative morphometric variables to fully characterise the benthic foraminiferal species concept of Elphidium williamsoni Haynes, 1973. A combination of live contemporary topotypic specimens, original type specimens and specimens of genetic outliers were utilised in this study. Through a series of multivariate statistical tests we illustrate that genetically characterised topotype specimens are morphologically congruent with both the holotype and paratype specimens of E. williamsoni Haynes, 1973. We present the first clear link between morphologically characterised type material and the unique SSU rRNA genetic type of E. williamsoni. This example provides a standard framework for the benthic foraminifera which bridges the current discontinuity between molecular and morphological lines of evidence, allowing integration with the traditional Linnaean roots of nomenclature to offer a new prospect for taxonomic stability.


Neural correlates of risk perception during real-life risk communication.
During global health crises, such as the recent H1N1 pandemic, the mass media provide the public with timely information regarding risk. To obtain new insights into how these messages are received, we measured neural data while participants, who differed in their preexisting H1N1 risk perceptions, viewed a TV report about H1N1. Intersubject correlation (ISC) of neural time courses was used to assess how similarly the brains of viewers responded to the TV report. We found enhanced intersubject correlations among viewers with high-risk perception in the anterior cingulate, a region which classical fMRI studies associated with the appraisal of threatening information. By contrast, neural coupling in sensory-perceptual regions was similar for the high and low H1N1-risk perception groups. These results demonstrate a novel methodology for understanding how real-life health messages are processed in the human brain, with particular emphasis on the role of emotion and differences in risk perceptions.


Common bean SNP alleles and candidate genes affecting photosynthesis under contrasting water regimes.
Water deficit is a major worldwide constraint to common bean (Phaseolus vulgaris L.) production, being photosynthesis one of the most affected physiological processes. To gain insights into the genetic basis of the photosynthetic response of common bean under water-limited conditions, a collection of 158 Portuguese accessions was grown under both well-watered and water-deficit regimes. Leaf gas-exchange parameters were measured and photosynthetic pigments quantified. The same collection was genotyped using SNP arrays, and SNP-trait associations tested considering a linear mixed model accounting for the genetic relatedness among accessions. A total of 133 SNP-trait associations were identified for net CO2 assimilation rate, transpiration rate, stomatal conductance, and chlorophylls a and b, carotenes, and xanthophyll contents. Ninety of these associations were detected under water-deficit and 43 under well-watered conditions, with only two associations common to both treatments. Identified candidate genes revealed that stomatal regulation, protein translocation across membranes, redox mechanisms, hormone, and osmotic stress signaling were the most relevant processes involved in common bean response to water-limited conditions. These candidates are now preferential targets for common bean water-deficit-tolerance breeding. Additionally, new sources of water-deficit tolerance of Andean, Mesoamerican, and admixed origin were detected as accessions valuable for breeding, and not yet explored.


Formative research of a quick list for an automated self-administered 24-hour dietary recall.
Twenty-four-hour dietary recalls are used to collect high-quality dietary data. Because they require highly trained interviewers, recalls are expensive and impractical for large-scale nutrition research, leading to the use of food frequency questionnaires. We are developing a computer-based, self-administered 24-hour dietary recall for use by adults. Our goal is an easy-to-use, low-cost, publicly available, Web-enabled instrument that will include elements of the Automated Multiple Pass Method developed by the US Department of Agriculture, which uses five passes to enhance recall. The initial pass is called the "quick list" and allows respondents to report foods consumed the previous day freely, in any order, and without detail. Using a crossover design, we conducted initial formative pilot testing among 18 adults in a self-administered computer environment. We tested two versions of a "quick list" (the first Automated Multiple Pass Method pass) for remembering foods consumed the previous day: "unstructured" and "meal-based." Respondents showed a strong preference for the meal-based version (13 of 18), although positive features of both were identified. Chronological reporting was most common, although many foods were sporadically reported out of order. Versions did not appreciably differ in number of foods reported, moved, or deleted. Usability issues and preferences were also identified. If these developmental efforts prove successful, the use of affordable automated recalls could be valuable in clarifying diet-disease associations in observational epidemiologic studies and measuring dietary compliance in clinical trials. This pilot work illustrates the usefulness of formative cognitive and usability testing for questionnaire and software development.


The effects of the World Trade Center event on birth outcomes among term deliveries at three lower Manhattan hospitals.
The effects of prenatal exposure to pollutants from the World Trade Center (WTC) disaster on fetal growth and subsequent health and development of exposed children remain a source of concern. We assessed the impact of gestational timing of the disaster and distance from the WTC in the 4 weeks after 11 September on the birth outcomes of 300 nonsmoking women who were pregnant at the time of the event. They were recruited at delivery between December 2001 and June 2002 from three hospitals close to the WTC site. Residential and work addresses of all participants for each of the 4 weeks after 11 September 2001 were geocoded for classification by place and timing of exposure. Average daily hours spent at each location were based on the women's reports for each week. Biomedical pregnancy and delivery data extracted from the medical records of each mother and newborn included medical complications, type of delivery, length of gestation, birth weight, birth length, and head circumference. Term infants born to women who were pregnant on 11 September 2001 and who were living within a 2-mile radius of the WTC during the month after the event showed significant decrements in term birth weight (-149 g) and birth length (-0.82 cm), compared with infants born to the other pregnant women studied, after controlling for sociodemographic and biomedical risk factors. The decrements remained significant with adjustment for gestational duration (-122 g and -0.74 cm, respectively). Women in the first trimester of pregnancy at the time of the WTC event delivered infants with significantly shorter gestation (-3.6 days) and a smaller head circumference (-0.48 cm), compared with women at later stages of pregnancy, regardless of the distance of their residence or work sites from the WTC. The observed adverse effects suggest an impact of pollutants and/or stress related to the WTC disaster and have implications for the health and development of exposed children.


What is the clinical value of mHealth for patients?
Despite growing interest from both patients and healthcare providers, there is little clinical guidance on how mobile apps should be utilized to add value to patient care. We categorize apps according to their functionality (e.g. preventative behavior change, digital self-management of a specific condition, diagnostic) and discuss evidence for effectiveness from published systematic reviews and meta-analyses and the relevance to patient care. We discuss the limitations of the current literature describing clinical outcomes from mHealth apps, what FDA clearance means now (510(k)/de novo FDA clearance) and in the future. We discuss data security and privacy as a major concern for patients when using mHealth apps. Patients are often not involved in the development of mobile health guidelines, and professionals' views regarding high-quality health apps may not reflect patients' views. We discuss efforts to develop guidelines for the development of safe and effective mHealth apps in the US and elsewhere and the role of independent app reviews sites in identifying mHealth apps for patient care. There are only a small number of clinical scenarios where published evidence suggests that mHealth apps may improve patient outcomes.


Evaluation of appendiceal mucinous neoplasms with a new classification system and literature review.
Appendiceal mucinous neoplasms constitute a diagnostic spectrum ranging from adenoma to mucinous adenocarcinoma. To date, many classification systems have been proposed to reflect the histomorphological diversity of neoplasms in this range and their clinical correspondence, and also to form a common terminology between the pathologist and clinicians. The aim of this review is to provide an updated perspective on the pathological features of appendiceal mucinous neoplasms. Using the 2016 Modified Delphi Consensus Protocol (Delphi) and the Eighth Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 19 cases presented from June 2011 to December 2016 were evaluated and diagnosed with appendiceal mucinous neoplasia. According to the Delphi, non-carcinoid epithelial tumours of the appendix were categorized in eight histomorphological architectural groups. These groups are adenoma, serrated polyp, low-grade appendiceal mucinous neoplasm, high-grade appendiceal mucinous neoplasm, mucinous adenocarcinoma, poorly-differentiated adenocarcinoma with signet-ring, signet-ring cell carcinoma and adenocarcinoma. The most common symptom was right lower quadrant pain. The median age of these cases was 60±15 years. There was a preponderance of females (F/M: 15/4). In our re-evaluation, six cases were diagnosed as serrated polyp. There were 11 cases in the LAMN group and two cases in the mucinous adenocarcinoma group. Using the Delphi and the AJCC manual, there were many changes in the classification, evaluation and treatment of appendiceal mucinous neoplasms. These classification systems have facilitated the compatibility and communication of clinicians and pathologists and have guided clinicians on treatment methods.


Oxidation of antibacterial molecules by aqueous ozone: moiety-specific reaction kinetics and application to ozone-based wastewater treatment.
Ozone and hydroxyl radical (*OH) reaction kinetics were measured for 14 antibacterial compounds from nine structural families, to determine whether municipal wastewater ozonation is likely to result in selective oxidation of these compounds' biochemically essential moieties. Each substrate is oxidized by ozone with an apparent second-order rate constant, k''(O3,app) > 1 x 10(3) M(-1) s(-1), at pH 7, with the exception of N(4)-acetylsulfamethoxazole (K''(O3,app) is 2.5 x 102 M(-1) s(-1)). k''(O3,app) values (pH 7) for macrolides, sulfamethoxazole, trimethoprim, tetracycline, vancomycin, and amikacin appear to correspond directly to oxidation of biochemically essential moieties. Initial reactions of ozone with N(4)-acetylsulfamethoxazole, fluoroquinolones, lincomycin, and beta-lactams do not lead to appreciable oxidation of biochemically essential moieties. However, ozone oxidizes these moieties within fluoroquinolones and lincomycin via slower reactions. Measured k''(O3,app) values and second-order *OH rate constants, k''(*OH,app) were utilized to characterize pollutant losses during ozonation of secondary municipal wastewater effluent. These losses were dependent on k''(O3,app), but independent of k''(*OH,app). Ozone doses > or =3 mg/L yielded > or =99% depletion of fast-reacting substrates (K''(O3,app) > 5 x 10(4) M(-1) s(-1)) at pH 7.7. Ten substrates reacted predominantly with ozone; only four were oxidized predominantly by .OH. These results indicate that many antibacterial compounds will be oxidized in wastewater via moiety-specific reactions with ozone.


Impairments in spatial navigation during walking in patients 70 years or younger with mild stroke.
Background: Spatial navigation, the ability to determine and maintain a route from one place to another, is needed for independence in everyday life. Knowledge about impairments in spatial navigation in people with mild stroke is scarce.Objectives: To explore impairments in spatial navigation in patients ≤70 years after first-ever mild ischemic stroke (NIHSS≤3) and to explore which variables are associated with these impairments 12 months later.Methods: Patients were examined in the acute phase, and after 3 and 12 months. To assess impairments in spatial navigation, we used the Floor Maze Test (FMT), with time and FMT-errors as outcomes. Patients' perceived navigational skills were collected using self-report. Logistic regression was used to explore which variables (sociodemographic data, stroke characteristics, cognition, and mobility) were associated with impaired navigation ability.Results: Ninety-seven patients (20 females) were included. The mean (SD) age was 55.5 (11.4) years. Timed FMT improved significantly from the acute phase to 12 months (p = <.001). At 12 months, 24 (24.7%) of the participants walked through the maze with errors, and 22 (22.7%) reported spatial navigational problems. The Trail Making Test (TMT)-B was the only variable from the acute phase associated with FMT-errors at 12 months, and being female was the only variable associated with self-reported navigational problems at 12 months.Conclusion: Nearly one in four patients experienced spatial navigation problems 12 months after a mild stroke. Executive function (TMT-B), measured in the acute phase, was associated with navigational impairments (FMT-errors) at 12 months, and being female was associated with self-reported navigational problems.


A selected reaction monitoring (SRM)-based method for absolute quantification of Aβ38, Aβ40, and Aβ42 in cerebrospinal fluid of Alzheimer's disease patients and healthy controls.
Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in research centers, clinical trials, and clinical settings. However, their broad-scale use is hampered by lack of standardization across analytical platforms and by interference from binding of amyloid-β (Aβ) to matrix proteins as well as self-aggregation. Here, we report on a matrix effect-resistant method for the measurement of the AD-associated 42 amino acid species of Aβ (Aβ42), together with Aβ40 and Aβ38 in human CSF based on mass spectrometric quantification using selected reaction monitoring (SRM). Samples were prepared by solid-phase extraction and quantification was performed using stable-isotope labeled Aβ peptides as internal standards. The diagnostic performance of the method was evaluated on two independent clinical materials with research volunteers who were cognitively normal and AD patients with mild to moderate dementia. Analytical characteristics of the method include a lower limit of quantification of 62.5 pg/mL for Aβ42 and coefficients of variations below 10%. In a pilot study on AD patients and controls, we verified disease-association with decreased levels of Aβ42 similar to that obtained by ELISA and even better separation was obtained using the Aβ42/Aβ40 ratio. The developed assay is sensitive and is not influenced by matrix effects, enabling absolute quantification of Aβ42, Aβ40, and Aβ38 in CSF, while it retains the ability to distinguish AD patients from controls. We suggest this SRM-based method for Aβ peptide quantification in human CSF valuable for clinical research and trials.


Medical education in an electronic health record-mediated world.
This paper reflects on the extent to which we are preparing learners for practice in an electronic health record (EHR)-mediated world. We are currently training the last generation to remember a world without the Internet and the first who will practice in a largely EHR-mediated practice environment. We undertook a thematic review of the literature connecting medical education with e-health using the concepts of 'electronic health record' or 'electronic medical record' as a proxy for the broader notion of e-health. Our findings are more equivocal and cautious than earlier commentators might have expected and while there are examples of good practice and successful integration, the majority of articles we reviewed raised issues and problems with the current links between EHRs and medical education. Medical professionals in particular are quite ambivalent about many of the changes brought about by EHRs, and in the absence of changes in perception and practice it is likely that the connections between medical education and e-health will continue to be problematic. We hope that this paper will lead to an improved understanding of these problems and will serve to advance the discourse on how medical education should engage with the world of e-health and the world of e-health with medical education.


High countrate real-time FCS using F2Cor.
We present a fluorescence correlation spectroscopy setup based on a software correlator. The setup can process autocorrelation curves in real-time at countrate as high as 8 MHz, with time resolution of 1 µs. It uses the F2Cor autocorrelation algorithm, a low cost counting board and a desktop computer. Symmetrical normalization, which improves the signal to noise ratio of the FCS curve for large values of the lag-time, is adapted to the F2Cor algorithm. A new acquisition mode, which we call oscilloscope-mode, is presented. It takes advantage of the flexibility F2Cor, and proves to be very useful for optical setup adjustment. As an application of this setup, we performed FCS measurements on a reference tetramethylrhodamine solution at high concentration, up to 2.5 µM, which extend to the micromolar range the concentration applicable in FCS, using a conventional optical setup. At such high countrates the FCS curves need to be corrected for dead-time of the photo-detector, which was done successfully.


Conceptions of agency and constraint for HIV-positive patients and healthcare workers to support long-term engagement with antiretroviral therapy care in Khayelitsha, South Africa.
In the context of the optimism around antiretroviral therapy (ART) as prevention of HIV/AIDS, addressing the barriers to long-term ART adherence is critical. This is particularly important given the tendency to individualise or use a blame discourse when exploring why HIV-infected patients "fail" to adequately adhere to ART, and not sufficiently exploring contextual reasons for poor adherence that may require varying solutions. This study took place at three clinics and one hospital in Khayelitsha, South Africa, to document the contextual factors that challenged ART adherence in this community. Interviews were conducted with 20 HIV-infected patients who had defaulted on their ART and were subsequently admitted to Khayelitsha hospital for clinical complications, and 9 ART service providers including doctors, nurses and HIV counsellors. Interviews assessed the reasons patients defaulted on ART and explored ways this could be prevented. Data from both groups were analysed collectively using thematic analysis. While the interviews revealed a landscape of environmental risks threatening adherence to ART, all patients managed to overcome the identified barriers at some point in their treatment phase, indicating the fluidity of patients' needs and decision making. Patients reported that distrustful relationships with service providers could inhibit their understanding of ART and/or interrupt their follow-up at clinics. Patients described their rationale and agency underlying non-adherence, such as testing their bodies' physical limits without ART medication. The study speaks to the need to appreciate contextual social and structural barriers related to ART adherence, and how these are negotiated differently by specific sub-groups, to support an appropriate response. It is imperative to not solely emphasise loss to follow-up but also assess patients' subjective trajectory of their ART journey, decision making and agency with adhering to ART, their relations with healthcare workers, and how these dynamics are intertwined with broader constraints in health systems.


Protocol for the induction of arthritis in C57BL/6 mice.
Collagen-induced arthritis is a well-validated, but strain-dependent mouse model of rheumatoid arthritis, with H-2(q) and H-2(r) strains showing the greatest degree of susceptibility. This protocol describes the induction of arthritis in the C57BL/6 strain (H-2(b)), which forms the genetic background of the majority of genetically modified strains. This protocol involves purification of type II collagen from chicken sternums, immunization of mice, clinical assessment of arthritis and analysis of T- and B-cell responses to type II collagen. Key aspects of the protocol are the need to use chicken collagen for immunization and the importance of avoiding aggressive behavior in males. The incidence of arthritis varies from 50 to 80% and is milder than the classical collagen-induced arthritis model. This procedure takes approximately 3 months to complete.


"It All Starts With the Parents": A Qualitative Study on Protective Factors for Drug-Use Prevention Among Black and Hispanic Girls.
Using intersectionality theory as a theoretical framework, this qualitative study uncovered the protective factors present among black and Hispanic adolescent girls living in an urban, under-resourced neighborhood in the Northeastern United States. The sample used in this study includes eight focus groups that consisted of adolescent females only (N = 57). Female participants were sampled through six youth-serving summer programs throughout the target city. The female participants were between 11 and 17 years of age, with 73% self-identifying as black (n = 45) and 26% (n = 12) as Hispanic. Thematic analysis using an intersectional approach was used to analyze the narratives of participants in the study. Three main themes arose: environmental context, parent-child communication about drug use, and parental modeling. Participants were critically aware of their environmental context which normalized drug use. However, participants identified protective factors such as parents communicating about drug use and parental modeling to girls in the sample as the most salient factors against substance use in their community. Findings provide insight for researchers, social workers, and interventionists to create and implement family-centered, strengths-based substance-abuse prevention programs that are racial, ethnic, and gender specific for black and Hispanic adolescent girls.


Impact of an Electronic Health Record (EHR) Reminder on Human Papillomavirus (HPV) Vaccine Initiation and Timely Completion.
The initiation and timely completion of the human papillomavirus (HPV) vaccine in young women is critical. We compared the initiation and completion of the HPV vaccine among women in 2 community-based networks with electronic health records: 1 with a prompt and reminder system (prompted cohort) and 1 without (unprompted cohort). Female patients aged 9 to 26 years seen between March 1, 2007, and January 25, 2010, were used as the retrospective cohort. Patient demographics and vaccination dates were extracted from the electronic health records. Patients eligible for the vaccine included 6019 from the prompted cohort and 9096 from the unprompted cohort. Mean age at initiation was 17.3 years in the prompted cohort and 18.1 years in the unprompted cohort. Significantly more (P < .001) patients initiated the vaccine in the prompted cohort (34.9%) compared with the unprompted cohort (21.5%). African Americans aged 9 to 18 years with ≥3 visits during the observation period were significantly more likely to initiate in the prompted cohort (P < .001). The prompted cohort was significantly more likely (P < .001) to complete the vaccine series in a timely manner compared with the unprompted cohort. More patients aged 9 to 26 years initiated and achieved timely completion of the HPV vaccine series in clinics using an electronic health record system with prompts compared with clinics without prompts.


Positive emotional well-being, health Behaviors, and inflammation measured by C-Reactive protein.
There is a substantial body of literature describing the association between inflammatory biomarkers and negative emotional factors (i.e. depression). However, less is known about how they might be related to positive psychological variables. This study examined the association between positive emotional well-being (PEWB) and C-Reactive Protein (CRP), an inflammatory biomarker important for cardiovascular and other diseases. Data were analyzed from 1979 respondents to a nationwide survey in the U.S., which included a chronically ill subgroup. Two aspects of PEWB were assessed; positive affect and life satisfaction. CRP was analyzed via blood-spot from a finger-prick. The mediating role of health behaviors (i.e., smoking, alcohol, BMI, and moderate exercise) was also examined. Both positive affect and life satisfaction were significantly related to lower CRP even after controlling for demographics and depression, in both the overall sample and chronically ill group. Only life satisfaction remained significantly related to CRP when controlling for health behaviors. When both depression and health behaviors were controlled, neither positive affect nor life satisfaction was significantly related to CRP. Moderate exercise emerged as the strongest mediator, followed by BMI and smoking. Individuals with low positive affect or low life satisfaction were at increased odds (OR = 1.40 and OR = 1.54, respectively) of having clinically elevated (≥3 mg/L) CRP. Our results add to a growing literature reporting an association between aspects of PEWB, especially life satisfaction, and a health-related biomarker of inflammation. Those with low positive affect or life satisfaction face increased risk of having clinically elevated CRP. Health behaviors, especially BMI and moderate exercise, account for some but not all of this relationship. Future studies should determine whether increasing life satisfaction and positive affect may contribute to improvements in health behaviors, inflammation, and better health outcomes.


A Pilot Primary Stroke Prevention Program for Elderly Korean Americans.
Stroke is a significant health issue with devastating consequences among older adults in the United States. However, it can be prevented by improving stroke knowledge and managing risk factors. Many stroke education programs have been shown to be effective. Unfortunately, a minority of older adults, such as older Korean Americans, have not benefited from the programs because of language barriers. The purpose of this study was to examine the feasibility and preliminary impact of a primary stroke prevention program on stroke knowledge, healthy eating, and physical activity behaviors among Korean Americans. A randomized controlled pilot trial was conducted. A total of 73 persons were randomly assigned to either an intervention group (n = 37) or a control group (n = 36). The intervention program included in-person lectures and discussions. Sociodemographic data were analyzed using descriptive statistics. Analyses of covariance and logistic regression analysis were used to evaluate the effects of the intervention program. The mean age of participants was 71.49 ± 6.25 years, and most participants were female (74.0%) and married (65.8%). Upon intervention completion, the intervention group showed greater improvements than the control group in stroke knowledge and intake of sodium and total fats (F = 11.89, P = .001, ηp = 0.151; F = 4.04, P = .048, ηp = 0.057; and F = 4.51, P = .037,= ηp = 0.062, respectively). Step counts showed marginal effects (F = 3.27, P = .075, ηp = 0.049). This study demonstrated feasibility and effectiveness of the program to improve stroke knowledge and healthy behaviors in elderly Korean Americans.


Shyness and timidity in young adults who were born at extremely low birth weight.
Recent studies have noted personality differences among adult survivors of very preterm birth, including higher neuroticism and cautiousness and lower extraversion. We attempted to replicate and extend these recent studies by examining personality characteristics across multiple components of personality that traditionally define personality structure in a birth cohort of young adults born at extremely low birth weight (501-1000 g), the smallest and most at-risk infants. We assessed 71 (76% of the original birth cohort) extremely low birth weight and 83 (74% of the original cohort) term normal birth weight young adults by using well-validated personality measures, indexing 4 traditional components of personality: temperament (Cheek and Buss shyness and sociability and Eysenck neuroticism and extraversion), motivation (Carver and White behavioral inhibition and behavioral activation), cognitive and affective (Coopersmith self-esteem and University of California, Los Angeles, loneliness), and socialization (Eysenck psychoticism and lie). All of the participants were right-handed and free of neurosensory and psychiatric impairments. Extremely low birth weight adults reported significantly higher shyness, behavioral inhibition, and socialization (a measure of prosocial behavior defined by risk aversion and adherence to societal mores) and lower sociability and emotional well-being than their normal birth weight counterparts, replicating and extending the findings of previous studies. Young adults who were born at extremely low birth weight and without major impairments are more cautious, shy, and risk aversive and less extraverted than their normal birth weight counterparts, possibly placing them at risk for future psychiatric and emotional problems.


Scene categorization in the presence of a distractor.
Humans display a very good understanding of the content in briefly presented photographs. To achieve this understanding, humans rely on information from both high-acuity central vision and peripheral vision. Previous studies have investigated the relative contribution of central and peripheral vision. However, the role of attention in this task remains unclear. In this study, we presented composite images with a scene in the center and another scene in the periphery. The two channels conveyed different information, and the participants were asked to focus on one channel while ignoring the other. In two experiments, we showed that (a) people are better at recognizing the central part, (b) the conflicting signal in the ignored part hinders performance, and (c) this effect is true for both parts (focusing on the central or peripheral part). We conclude that scene recognition is based on both central and peripheral information, even when participants are instructed to focus only on one part of the image and ignore the other. In contrast to the zoom-out hypothesis, we propose that the gist recognition process should be interpreted in terms of the evidence accumulation model in which information from the to-be-ignored parts is also included.


Hepatic Bmal1 Regulates Rhythmic Mitochondrial Dynamics and Promotes Metabolic Fitness.
Mitochondria undergo architectural/functional changes in response to metabolic inputs. How this process is regulated in physiological feeding/fasting states remains unclear. Here we show that mitochondrial dynamics (notably fission and mitophagy) and biogenesis are transcriptional targets of the circadian regulator Bmal1 in mouse liver and exhibit a metabolic rhythm in sync with diurnal bioenergetic demands. Bmal1 loss-of-function causes swollen mitochondria incapable of adapting to different nutrient conditions accompanied by diminished respiration and elevated oxidative stress. Consequently, liver-specific Bmal1 knockout (LBmal1KO) mice accumulate oxidative damage and develop hepatic insulin resistance. Restoration of hepatic Bmal1 activities in high-fat-fed mice improves metabolic outcomes, whereas expression of Fis1, a fission protein that promotes quality control, rescues morphological/metabolic defects of LBmal1KO mitochondria. Interestingly, Bmal1 homolog AHA-1 in C. elegans retains the ability to modulate oxidative metabolism and lifespan despite lacking circadian regulation. These results suggest clock genes are evolutionarily conserved energetics regulators.


Eating Disorders: Identification and Management in General Medical and Psychiatric Settings.
Eating disorders (EDs) are serious, complex illnesses with both behavioral and physical health features. EDs have high rates of medical and psychiatric morbidity, and a 6% mortality rate, the highest of any mental illness. Early detection of EDs offers the best opportunity for recovery; yet, estimates are that as few as one in 10 individuals with an ED receive treatment. The purpose of this article is to provide an ED identification and management overview for inpatient nurse clinicians in general psychiatric and medical settings, helping to facilitate timely recognition and care. An overview of ED diagnostic criteria and two evidence-based ED tools are introduced for consideration. Opportunities to identify and help manage an ED are numerous. Most individuals with an ED make several health care visits in either medical or psychiatric settings without ever being screened for an ED. General ED screening and assessment tool familiarization can facilitate a treatment trajectory for these patients, improve overall quality of life, and may potentially result in a life-saving intervention for this often-deadly cluster of medical and psychiatric disorders. Screening and assessment in general clinical settings, identifying patients with undiagnosed EDs, beginning basic treatment plans, and referrals for appropriate follow-up care, have the potential to reduce ED recidivism and related health care costs. Simultaneously, and most important, long-term outcomes for patients with EDs may improve.


Treatment of substance-related problems in Switzerland: implementing a new harmonised monitoring system.
In the past, five different monitoring systems were used in the various areas of the care supply for substance-related problems in Switzerland, without any real coordination between them. In 1999, a project aiming at the harmonisation of these five monitoring systems was launched by federal agencies. A further aim was to ensure compatibility with the Treatment Demand Indicator (TDI) adopted as European standard. The different steps of the conceptualisation process and their rationales are described. They involve a first phase of consultation among all key players, a second phase of preliminary realisation according to the target criteria, a third phase of probation by the application of a pilot survey, and a last phase of consolidation and adjustments before the official implementation. A comprehensive and flexible monitoring system was settled for all fields of the addiction care in Switzerland. It consists of a fully standardised pool of core items to be shared by the five treatment sectors as well as optional items intended for specific needs. The practical aspects of the implementation, like data protection, organisation of data collection, and valorisation of the results are presented. The first experiences in the different treatment sectors are also reported. The implementation of "act-info" is still an ongoing process that began in 2003. Since 2005, the new monitoring system is well implemented in three out of five treatment sectors, whereas its introduction proves more challenging in the two remaining sectors. Perspectives of improvement regarding coverage and data quality are proposed.


Intracellular delivery of top-down fabricated tunable nano-plasmonic resonators.
Engineered plasmonic structures fabricated using top-down technologies have demonstrated huge enhancements in the optical response of molecules, including Raman scattering. However, providing a sufficient number of such top-down fabricated nanostructures in solution has been a nontrivial task which has limited their potential in intracellular applications. Here we report the development of a protocol for the intracellular delivery of tunable nanoplasmonic resonators fabricated via scalable top-down techniques. This offers excellent possibilities towards the real-time parallel optical detection of intracellular molecular events.


Developmental regulation of the gibberellin pathway in pea shoots.
To investigate gibberellin (GA) biosynthesis in mature tissue of pea (Pisum sativum L.) in the absence of potentially GA-producing meristematic tissue we grafted wild-type scions to rootstocks of the GA-deficient ls-1 mutant and later decapitated the shoot. After 2 d, decapitated shoots contained as much GA19 (a precursor of the bioactive GA1) as comparable tissue from intact plants, even though applied [14C]GA19 was metabolised rapidly during this time. These results show that the pool size of endogenous GA19 was maintained, probably by de novo GA19 synthesis. We also found that the LS gene, which catalyses an early step in GA biosynthesis, is expressed in mature tissue, as are the shoot-expressed GA 20-oxidase and GA 3-oxidase genes. Nevertheless, mature tissue contained very low levels of GA1 and GA20 compared with immature tissue. Levels of GA19, GA29 and GA8 were less affected by tissue age. Metabolism studies using 14C-labelled GAs indicated that mature tissue rapidly converted GA19 to GA20 and GA20 to GA1; the latter step was promoted by IAA. However, the 2-oxidation steps GA1 to GA8, GA20 to GA29 and GA29 to GA29-catabolite appear to proceed very rapidly in mature tissue (regardless of IAA content), and we suggest this is the reason why GA1 and GA20 do not accumulate. This is supported by the high level of expression of a key GA 2-oxidase gene in mature tissue.


The nuts and bolts of subcutaneous insulin therapy in non-critical care hospital settings.
In non-critical care settings, patients with hyperglycemia experience increased morbidity and mortality. Despite an increased recognition of the importance of treating inpatient hyperglycemia, many patients are still not adequately controlled. Insulin offers flexibility to address varying glucose levels and therefore is the preferred therapy to achieve recommended targets and manage hyperglycemia. Traditional sliding-scale insulin regimens often ineffectively control blood glucose levels as they are unable to mimic physiologic insulin secretion. Basal-bolus insulin regimens are recognized as a more effective way to correct hyperglycemia in non-critical care settings and a systematic glycemic control program is necessary to address hyperglycemia while minimizing hypoglycemia. Critical components of these programs include addressing barriers to glycemic control, understanding varying needs of different types of patients, and developing standardized subcutaneous insulin orders to achieve target glucose levels. This article provides strategies for using insulin in non-critical care settings to facilitate glycemic control.


Modeling a linkage between blood transcriptional expression and activity in brain regions to infer the phenotype of schizophrenia patients.
Hundreds of genetic loci participate to schizophrenia liability. It is also known that impaired cerebral connectivity is directly related to the cognitive and affective disturbances in schizophrenia. How genetic susceptibility and brain neural networks interact to specify a pathological phenotype in schizophrenia remains elusive. Imaging genetics, highlighting brain variations, has proven effective to establish links between vulnerability loci and associated clinical traits. As previous imaging genetics works in schizophrenia have essentially focused on structural DNA variants, these findings could be blurred by epigenetic mechanisms taking place during gene expression. We explored the meaningful links between genetic data from peripheral blood tissues on one hand, and regional brain reactivity to emotion task assayed by blood oxygen level-dependent functional magnetic resonance imaging on the other hand, in schizophrenia patients and matched healthy volunteers. We applied Sparse Generalized Canonical Correlation Analysis to identify joint signals between two blocks of variables: (i) the transcriptional expression of 33 candidate genes, and (ii) the blood oxygen level-dependent activity in 16 region of interest. Results suggested that peripheral transcriptional expression is related to brain imaging variations through a sequential pathway, ending with the schizophrenia phenotype. Generalization of such an approach to larger data sets should thus help in outlining the pathways involved in psychiatric illnesses such as schizophrenia. SEARCHING FOR LINKS TO AID DIAGNOSIS: Researchers explore links between the expression of genes associated with schizophrenia in blood cells and variations in brain activity during emotion processing. El Chérif Ibrahim and Eric Fakra at Aix-Marseille Université, France, and colleagues have developed a method to relate the expression levels of 33 schizophrenia susceptibility genes in blood cells and functional magnetic resonance imaging (fMRI) data obtained as individuals carry out a task that triggers emotional responses. Although they found no significant differences in the expression of genes between the 26 patients with schizophrenia and 26 healthy controls they examined, variations in activity in the superior temporal gyrus were strongly linked to schizophrenia-associated gene expression and presence of disease. Similar analyses of larger data sets will shed further light on the relationship between peripheral molecular changes and disease-related behaviors and ultimately, aid the diagnosis of neuropsychiatric disease.


The general transcription-repair factor TFIIH is recruited to the excision repair complex by the XPA protein independent of the TFIIE transcription factor.
Recent studies have revealed that the general transcription factor TFIIH is also a general excision repair factor which, along with several other proteins, is required for transcription-independent excision reaction. As a general transcription factor, TFIIH is recruited to RNA polymerase II-promoter complex by another general transcription factor called TFIIE. We were interested in knowing whether TFIIE is also involved in recruiting TFIIH to the excision repair complex. We found that cell-free extract depleted of TFIIE carried out excision repair at a normal rate, leading us to conclude that TFIIE is not involved in recruiting TFIIH to the damage site and has no role in general excision repair. In contrast, the human damage recognition protein XPA specifically binds to TFIIH and apparently recruits it to the damage site. The carboxyl-terminal half of XPA is responsible for specific interaction with TFIIH. The C261S/C264S mutant of XPA bound the ERCC1-XPF complex normally, but failed to bind TFIIH and failed to complement an XP-A mutant cell-free extract indicating that the XPA-TFIIH interaction is essential to effecting the excision reaction. Interestingly, XPA also binds to the p34 subunit of TFIIE specifically and in competition with the p56 subunit of TFIIE. This latter interaction has no apparent role in general excision repair but may be relevant in the transcription-coupled repair reaction.


Adaptation to a novel family environment involves both apparent and cryptic phenotypic changes.
Cryptic evolution occurs when evolutionary change is masked by concurrent environmental change. In most cases, evolutionary changes in the phenotype are masked by changing abiotic factors. However, evolutionary change in one trait might also be masked by evolutionary change in another trait, a phenomenon referred to as evolutionary environmental deterioration. Nevertheless, detecting this second type of cryptic evolution is challenging and there are few compelling examples. Here, we describe a likely case of evolutionary environmental deterioration occurring in experimental burying beetle (Nicrophorus vespilloides) populations that are adapting to a novel social environment that lacks post-hatching parental care. We found that populations rapidly adapted to the removal of post-hatching parental care. This adaptation involved clear increases in breeding success and larval density (number of dispersing larvae produced per gram of breeding carcass), which in turn masked a concurrent increase in the mean larval mass across generations. This cryptic increase in larval mass was accomplished through a change in the reaction norm that relates mean larval mass to larval density. Our results suggest that cryptic evolution might be commonplace in animal families, because evolving trophic and social interactions can potentially mask evolutionary change in other traits, like body size.


Normal rainbow trout serum (RTS)-resistant variants of the infectious pancreatic necrosis virus (IPNV)-Jasper differ with respect to inhibition by RTS, serotype and cDNA sequence.
In order to determine if the infectious pancreatic necrosis virus isolate IPNV-Jasper (Ja-ATCC) is homogeneous or heterogeneous with respect to inhibition by normal rainbow trout serum (RTS), 50 clones were tested for sensitivity to RTS. The initial isolate was very sensitive to RTS, losing from 10(4) to 10(8) 50 % tissue culture infection dose (TCID50) ml(-1) with a 1:100 dilution of RTS. The sensitivity of the clones ranged from highly sensitive to completely resistant (0 to 10(8) TCID50 ml(-1) reduction). Eight percent of clones (4/50) were very sensitive to RTS (Ja-S) and 84% of clones (42/50) showed a mid-range of sensitivity to RTS. The final 8 % of clones (4/50) were resistant to RTS (Ja-R). Enzyme immunodot assay revealed that Ja-S clones showed a monoclonal reaction identical to the parents, Ja-ATCC; however, Ja-R clones differed by several epitopes from the parental strain. Analysis of Ja-S and Ja-R revealed that there were significant differences in their nucleic acid sequences for the capsid protein VP2. These 2 strains shared 80.7 and 86.5% identity in nucleic acid and in amino acid sequences, respectively. Ja-S had 99.7 and 91.0 % identity in nucleic acid sequences, and 99.5 and 95.9 % in amino acid sequences with Ja-ATCC and Jasper-Dobos (Ja-D), respectively, while Ja-R showed 80.6 and 79.8 % identity in nucleic acid sequences and 86.5 and 87.0 % in amino acid sequences with Ja-ATCC and Ja-D, respectively. In conclusion, the Ja-ATCC population was heterogeneous in terms of RTS sensitivity, serotype and cDNA sequences from the VP2 coding region.


Dynamics of temporal variations in phonatory flow.
This paper addresses the dynamic relevance of time variations of phonatory airflow, commonly neglected under the quasisteady phonatory flow assumption. In contrast to previous efforts, which relied on direct measurement of glottal impedance, this work uses spatially and temporally resolved measurements of the velocity field to estimate the unsteady and convective acceleration terms in the unsteady Bernoulli equation. Theoretical considerations suggest that phonatory flow is inherently unsteady when two related conditions apply: (1) that the unsteady and convective accelerations are commensurate, and (2) that the inertia of the glottal jet is non-negligible. Acceleration waveforms, computed from experimental data, show that unsteady and convective accelerations to be the same order of magnitude, throughout the cycle, and that the jet flow contributes significantly to the unsteady acceleration. In the middle of the cycle, however, jet inertia is negligible because the convective and unsteady accelerations nearly offset one another in the jet region. These results, consistent with previous findings treating quasisteady phonatory flow, emphasize that unsteady acceleration cannot be neglected during the final stages of the phonation cycle, during which voice sound power and spectral content are largely determined. Furthermore, glottal jet dynamics must be included in any model of phonatory airflow.


Cortical thickness and inattention/hyperactivity symptoms in young children: a population-based study.
While many neuroimaging studies have investigated the neurobiological basis of attention deficit hyperactivity disorder (ADHD), few have studied the neurobiology of attention problems in the general population. The ability to pay attention falls along a continuum within the population, with children with ADHD at one extreme of the spectrum and, therefore, a dimensional perspective of evaluating attention problems has an added value to the existing literature. Our goal was to investigate the relationship between cortical thickness and inattention and hyperactivity symptoms in a large population of young children. This study is embedded within the Generation R Study and includes 6- to 8-year-old children (n = 444) with parent-reported attention and hyperactivity measures and high-resolution structural imaging data. We investigated the relationship between cortical thickness across the entire brain and the Child Behavior Checklist Attention Deficit Hyperactivity Problems score. We found that greater attention problems and hyperactivity were associated with a thinner right and left postcentral gyrus. When correcting for potential confounding factors and multiple testing, these associations remained significant. In a large, population-based sample we showed that young (6- to 8-year-old) children who show more attention problems and hyperactivity have a thinner cortex in the region of the right and left postcentral gyrus. The postcentral gyrus, being the primary somatosensory cortex, reaches its peak growth early in development. Therefore, the thinner cortex in this region may reflect either a deviation in cortical maturation or a failure to reach the same peak cortical thickness compared with children without attention or hyperactivity problems.


Effectiveness of citronella preparations in preventing mosquito bites: systematic review of controlled laboratory experimental studies.
This review aims to examine the effectiveness of citronella preparation used as a mosquito repellent. Multiple computerized databases such as MEDLINE, EMBASE, Cochrane CENTRAL, CINAHL, and AMED, were searched for controlled laboratory experiments that compared the effectiveness of citronella products to control in repelling Aedes, Anopheles and Culex mosquitoes using the cage or room methods. Outcomes measures were protection time and percentage repellency. The weighted mean difference and 95% confidence interval were calculated comparing the outcomes in the citronella and control groups. Meta-analysis was performed using the DerSimonian and Laird method under a random-effects model. Eleven studies met inclusion criteria. Based on a meta-analysis of studies using the cage method, protection time of the citronella oil for preventing Aedes mosquitoes was less than that in the DEET (N,N-diethyl-m-toluamide) group, with a difference in protection time of 253 min (95% confidence interval: 169-336). The combination of citronella oil and vanillin is likely to have a longer protection time compared with citronella oil alone. In studies using the room method, citronella oil and/or the combination of citronella oil and vanillin provided complete repellency at least 3 h. In Anopheles and Culex mosquitoes, a combination of citronella oil and vanillin product demonstrated a comparable protection time against DEET; however, it remained inconclusive due to a limited number of studies. Citronella products are less effective than DEET products in terms of duration of protection. Adding vanillin to citronella oil products could prolong the protection time.


Clinically validated mutation scores for HIV-1 resistance to fosamprenavir/ritonavir.
We developed clinically relevant genotypic scores for resistance to fosamprenavir/ritonavir in HIV-1 protease inhibitor (PI)-experienced patients. PI-experienced patients with virological failure receiving fosamprenavir/ritonavir as the sole PI for at least 3 months and with detectable fosamprenavir plasma levels were included. The impact of baseline protease mutations on virological response (VR, i.e. decrease in plasma HIV-1 RNA between baseline and month 3) was analysed using the Mann-Whitney test. Mutations with prevalence >10% and P value <0.10 were retained. The Jonckheere-Terpstra test was used to select the combination of mutations most strongly associated with VR. The association between score and VR was assessed by multivariate backward regression. In the 73 patients included, the median baseline HIV-1 RNA was 4.6 log(10) copies/mL (range: 2.7-6.9) and the mean decrease at month 3 was -1.07 +/- 1.40 log(10) copies/mL. Ninety per cent of the patients were infected by HIV-1 subtype B variants. Two fosamprenavir/ritonavir mutation scores were constructed: score A (L10F/I/V + L33F + M36I + I54L/M/V/A/T/S + I62V + V82A/F/C/G + I84V + L90M) was based only on mutations associated with a worse VR, whereas score B (L10FIV + L33F + M36I + I54L/M/V/A/T/S + A71V - V77I - N88S + L90M) also took into account favourable mutations. Both scores were independent predictors of VR, however, co-administration of tenofovir was associated with a worse VR and the presence of the N88S protease mutation and co-administration of enfuvirtide with a better VR. These clinically validated mutation scores should be of interest for the clinical management of PI-experienced patients. The fosamprenavir/ritonavir score A was introduced in the 2006 ANRS algorithm along with isolated mutations I50V and V32I + I47V.


Charge-Mediated Pyrin Oligomerization Nucleates Antiviral IFI16 Sensing of Herpesvirus DNA.
The formation of multimerized protein assemblies has emerged as a core component of immune signal amplification, yet the biochemical basis of this phenomenon remains unclear for many mammalian proteins within host defense pathways. The interferon-inducible protein 16 (IFI16) is a viral DNA sensor that oligomerizes upon binding to nuclear viral DNA and induces downstream antiviral responses. Here, we identify the pyrin domain (PYD) residues that mediate IFI16 oligomerization in a charge-dependent manner. Based on structure modeling, these residues are predicted to be surface exposed within distinct α-helices. By generating oligomerization-deficient mutants, we demonstrate that IFI16 homotypic clustering is necessary for its assembly onto parental viral genomes at the nuclear periphery upon herpes simplex virus 1 (HSV-1) infection. Preventing oligomerization severely hampered the capacity of IFI16 to induce antiviral cytokine expression, suppress viral protein levels, and restrict viral progeny production. Restoring oligomerization via residue-specific charge mimics partially rescued IFI16 antiviral roles. We show that pyrin domains from PYHIN proteins are functionally interchangeable, facilitating cooperative assembly with the IFI16 HINs, highlighting an inherent role for pyrin domains in antiviral response. Using immunoaffinity purification and targeted mass spectrometry, we establish that oligomerization promotes IFI16 interactions with proteins involved in transcriptional regulation, including PAF1C, UBTF, and ND10 bodies. We further discover PAF1C as an HSV-1 restriction factor. Altogether, our study uncovers intrinsic properties that govern IFI16 oligomerization, which serves as a signal amplification platform to activate innate immune responses and to recruit transcriptional regulatory proteins that suppress HSV-1 replication.IMPORTANCE The ability of mammalian cells to detect the genomes of nuclear-replicating viruses via cellular DNA sensors is fundamental to innate immunity. Recently, mounting evidence is supporting the universal role of polymerization in these host defense factors as a signal amplification strategy. Yet, what has remained unclear are the intrinsic properties that govern their immune signal transmission. Here, we uncover the biochemical basis for oligomerization of the nuclear DNA sensor, IFI16. Upon infection with herpes simplex virus 1 (HSV-1) in human fibroblasts, we characterize the contribution of IFI16 oligomerization to downstream protein interactions and antiviral functions, including cytokine induction and suppression of HSV-1 replication. Until now, the global characterization of oligomerization-dependent protein interactions for an immune receptor has never been explored. Our integrative quantitative proteomics, molecular CRISPR/Cas9-based assays, mutational analyses, and confocal microscopy shed light on the dynamics of immune signaling cascades activated against pathogens.


Tracking energy transfer from excited to accepting modes: application to water bend vibrational relaxation.
We extend, via a reformulation in terms of Poisson brackets, the method developed previously (Rey et al., J. Phys. Chem. A, 2009, 113, 8949) allowing analysis of the pathways of an excited molecule's ultrafast vibrational relaxation in terms of intramolecular and intermolecular contributions. In particular we show how to ascertain, through the computation of power and work, which portion of an initial excess molecular energy (e.g. vibrational) is transferred to various degrees of freedom (e.g. rotational, translational) of the excited molecule itself and its neighbors. The particular case of bend excess energy relaxation in pure water is treated in detail, completing the picture reported in the work cited above. It is shown explicitly, within a classical description, that almost all of the initial water bend excitation energy is transferred-either indirectly, via Fermi resonance centrifugal coupling to the bend-excited water's rotation, or directly via intermolecular coupling- to local water librations, only involving molecules in the first two hydration shells of the vibrationally excited water molecule. Finally, it is pointed out that the Poisson bracket formulation can also be applied to elucidate the microscopic character of solvation and rotational dynamics, and should prove useful in developing a quantum treatment for energy flow in condensed phases.


Sodium-glucose Cotransporter 2 Inhibitors: Nephroprotective Impact on Diabetic Kidney Disease.
Diabetic nephropathy is a crucial microvascular complication of diabetes mellitus that is associated with elevated cardiovascular risk. SGLT-2 inhibitors are a new class of hypoglycemic drugs that positively affect several risk factors of cardiorenal damage. The study aimed to review and critically discuss available data on the association of SGLT-2 inhibitors treatment with kidney function, progress of diabetic kidney disease, and renal related outcomes, as well to unveil potential mechanisms of action that mediate such effects. We conducted a comprehensive search of the literature on the renal related effects of SGLT-2 inhibitors, to compose a narrative mini-review. The administration of SGLT-2 inhibitors was observed to exert beneficial effects on a wide cluster of risk factors of chronic kidney disease, such as hyperglycemia, blood pressure, serum uric acid, and body weight. Data from the first two large, randomized, clinical trials of SGLT-2 inhibitors conducted to address the renal related outcomes of SGLT-2 inhibitors suggest substantial benefits on estimated glomerular filtration rate decline and albuminuria. The initial data suggest clinically meaningful benefits of the SGLT-2 inhibitors in diabetic patients in relevance with chronic kidney disease. Future, well-designed randomised clinical trials need to be further investigated such as nephroprotective outcomes, that if confirmed, could lead to new perspectives in the management of diabetic nephropathy.


Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials.
To explore the extent to which components of composite end points in randomised controlled trials vary in importance to patients, the frequency of events in the more and less important components, and the extent of variability in the relative risk reductions across components. Systematic review of randomised controlled trials. Cardiovascular randomised controlled trials published in the Lancet, Annals of Internal Medicine, Circulation, European Heart Journal, JAMA, and New England Journal of Medicine, from 1 January 2002 to 30 June 2003. Component end points of composite end points were categorised according to importance to patients as fatal, critical, major, moderate, or minor. Of 114 identified randomised controlled trials that included a composite end point of importance to patients, 68% (n=77) reported complete component data for the primary composite end point; almost all (98%; n=112) primary composite end points included a fatal end point. Of 84 composite end points for which component data were available, 54% (n=45) showed large or moderate gradients in both importance to patients and magnitude of effect across components. When analysed by categories of importance to patients, the most important components were associated with lower event rates in the control group (medians of 3.3-3.7% for fatal, critical, and major outcomes; 12.3% for moderate outcomes; and 8.0% for minor outcomes). Components of greater importance to patients were associated with smaller treatment effects than less important ones (relative risk reduction of 8% for death and 33% for components of minor importance to patients). The use of composite end points in cardiovascular trials is frequently complicated by large gradients in importance to patients and in magnitude of the effect of treatment across component end points. Higher event rates and larger treatment effects associated with less important components may result in misleading impressions of the impact of treatment.


Inhibition of Rac1-derived reactive oxygen species in nucleus tractus solitarius decreases blood pressure and heart rate in stroke-prone spontaneously hypertensive rats.
Reactive oxygen species (ROS) in the brain are thought to contribute to the neuropathogenesis of hypertension by enhancing sympathetic nervous system activity. The nucleus tractus solitarius (NTS), which receives afferent input from baroreceptors, has an important role in cardiovascular regulation. reduced nicotinamide-adenine dinucleotide phosphate oxidase is thought to be a major source of ROS in the NTS. Rac1 is a small G protein and a key component of reduced nicotinamide-adenine dinucleotide phosphate oxidase. The role of Rac1-derived ROS in the NTS in cardiovascular regulation of hypertension is unknown. Therefore, we examined whether inhibition of Rac1 in the NTS decreases ROS generation, thereby reducing blood pressure in stroke-prone spontaneously hypertensive rats (SHRSPs). The basal Rac1 activity level in the NTS was greater in SHRSPs than in Wistar-Kyoto rats. Inhibition of Rac1, induced by transfecting adenovirus vectors encoding dominant-negative Rac1 into the NTS, decreased blood pressure, heart rate, and urinary norepinephrine excretion in SHRSPs but not in Wistar-Kyoto rats. Inhibition of Rac1 also reduced nicotinamide-adenine dinucleotide phosphate oxidase activity and ROS generation. In addition, Cu/Zn-superoxide dismutase activity in the NTS of SHRSPs was decreased compared with that of Wistar-Kyoto rats, despite the increased ROS generation. Overexpression of Cu/Zn-superoxide dismutase in the NTS decreased blood pressure and heart rate in SHRSPs. These results indicate that the activation of Rac1 in the NTS generates ROS via reduced nicotinamide-adenine dinucleotide phosphate oxidase in SHRSPs, and this mechanism might be important for the neuropathogenesis of hypertension in SHRSPs.


Rehearsing biological motion in working memory: an EEG study.
Holding biological motion (BM), the movements of animate entities, in working memory (WM) is important to our daily social life. However, how BM is maintained in WM remains unknown. The current study investigated this issue and hypothesized that, analogous to BM perception, the human mirror neuron system (MNS) is involved in rehearsing BM in WM. To examine the MNS hypothesis of BM rehearsal, we used an EEG index of mu suppression (8-12 Hz), which has been linked to the MNS. Using a change detection task, we manipulated the BM memory load in three experiments. We predicted that mu suppression in the maintenance phase of WM would be modulated by the BM memory load; moreover, a negative correlation between the number of BM stimuli in WM and the degree of mu suppression may emerge. The results of Experiment 1 were in line with our predictions and revealed that mu suppression increased as the memory load increased from two to four BM stimuli; however, mu suppression then plateaued, as WM could only hold, at most, four BM stimuli. Moreover, the predicted negative correlation was observed. Corroborating the findings of Experiment 1, Experiment 2 further demonstrated that once participants used verbal codes to process the motion information, the mu suppression or modulation by memory load vanished. Finally, Experiment 3 demonstrated that the findings in Experiment 1 were not limited to one specific type of stimuli. Together, these results provide evidence that the MNS underlies the process of rehearsing BM in WM.


Phosphatidylinositol-phospholipase C2 regulates pattern-triggered immunity in Nicotiana benthamiana.
Phospholipid signaling plays an important role in plant immune responses against phytopathogenic bacteria in Nicotiana benthamiana. Here, we isolated two phospholipase C2 (PLC2) orthologs in the N. benthamiana genome, designated as PLC2-1 and 2-2. Both NbPLC2-1 and NbPLC2-2 were expressed in most tissues and were induced by infiltration with bacteria and flg22. NbPLC2-1 and NbPLC2-2 (NbPLC2s) double-silenced plants showed a moderately reduced growth phenotype. The induction of the hypersensitive response was not affected, but bacterial growth and the appearance of bacterial wilt were accelerated in NbPLC2s-silenced plants when they were challenged with a virulent strain of Ralstonia solanacearum that was compatible with N. benthamiana. NbPLC2s-silenced plants showed reduced expression levels of NbPR-4, a marker gene for jasmonic acid signaling, and decreased jasmonic acid and jasmonoyl-L-isoleucine contents after inoculation with R. solanacearum. The induction of pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) marker genes was reduced in NbPLC2s-silenced plants after infiltration with R. solanacearum or Pseudomonas fluorescens. Accordingly, the resistance induced by flg22 was compromised in NbPLC2s-silenced plants. In addition, the expression of flg22-induced PTI marker genes, the oxidative burst, stomatal closure, and callose deposition were all reduced in the silenced plants. Thus, NbPLC2s might have important roles in pre- and post-invasive defenses, namely in the induction of PTI.


Influenza vaccination: healthcare workers attitude in three Middle East countries.
Healthcare workers (HCWs) pose a potential risk of transmitting communicable diseases in the hospital settings where they usually work. This study aims to determine the current influenza vaccination rates among HCWs in three Middle East countries namely United Arab Emirates (UAE), Kuwait and Oman, and also to identify the different variables associated with the noncompliance of HCWs to the recommendations of the Advisory Committee on Immunization Practices (ACIP) set in those countries. 1500 questionnaires were distributed to health care workers in the three countries during the period of July-October 2009. Among 993 respondents, the vaccination rate was 24.7%, 67.2% and 46.4% in UAE, Kuwait and Oman, respectively. The different motivating factors that influenced the health care workers to take the vaccine was assessed and found that the most common factor that influenced their decision to take the vaccine was for their self protection (59%). On the other hand, the most common reason that discouraged HCWs to take the vaccine was "lack of time" as reported by 31.8% of the respondents. Other reasons for not taking the vaccine were unawareness of vaccine availability (29.4%), unavailability of vaccine (25.4%), doubts about vaccine efficacy (24.9%), lack of information about importance (20.1%) and concerns about its side effects (17.3%). influenza immunization by healthcare workers in the studied countries was suboptimal which could be improved by setting different interventions and educational programs to increase vaccination acceptance among HCWs.


Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline.
The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.


Progesterone reverses the spatial memory enhancements initiated by tonic and cyclic oestrogen therapy in middle-aged ovariectomized female rats.
While some research has indicated that ovarian hormone therapy (HT) benefits memory and decreases risk of Alzheimer's disease in menopausal women, several newer studies have shown null or detrimental effects. Despite the null and negative cognitive findings, the numerous studies showing positive effects beg the question of what factors determine whether HT acts as a neuroprotectant or a risk factor for brain functioning. Using middle-aged female rats, we directly compared six HTs. We evaluated the effects of ovariectomy, tonic low-dose, tonic high-dose and biweekly cyclic estradiol treatment, as well as whether progesterone altered the effectiveness of any one of these oestrogen regimens. Animals were tested on spatial and complex cued (intramaze patterns) reference memory using variants of the Morris maze. The tonic low-dose and cyclic estradiol treatments improved spatial performance, while the addition of progesterone reversed these beneficial cognitive effects of estradiol. Additionally, all groups learned to locate the platform on the cued task; however, an egocentric circling strategy was used with sham ovary-intact and hormone-replacement groups showing the most efficient search strategy. Although the question of memory retention 8 weeks after the first cognitive assessment was addressed, a large number of animals died between the first and second test, rendering the retest uninterpretable for many group comparisons. Specifically, both doses of tonic estradiol dramatically increased the number of deaths during the 17-week experiment, while the cyclic estradiol treatment did not. Progesterone decreased the number of deaths due to tonic estradiol treatment. Our findings suggest that the dose of estradiol replacement as well as the presence of progesterone influences the cognitive outcome of estradiol treatment. Further, there appears to be a dissociation between HT effects on cognition and mortality rates.


Can novel adipokines, asprosin and meteorin-like, be biomarkers for malignant mesothelioma?
Malignant mesothelioma (MM) is a rare tumor of serous surfaces that has a poor prognosis. Cancer is a multistage process by which cells undergo metabolic and behavioral changes that cause excessive and untimely proliferation. Asprosin (ASP) and meteorin-like (METRNL) are two peptides associated with glucose and energy metabolism. We used immunohistochemistry to investigate whether these peptides could be biomarkers for diagnosis and treatment of MM. We reviewed 30 cases of MM and 30 cases of reactive mesothelial hyperplasia (RMH); we used the cases with RMH as control group. The specimens were examined using immunohistochemical staining for ASP and METRNL. ASP and METRNL immunoreactivity was more prominent in the MM specimens than the RMH specimens. Therefore, ASP and METRNL potentially could be used as markers for differentiating MM from benign diseases.


Simultaneous immunization against tuberculosis.
BCG, the only licensed vaccine against tuberculosis, provides some protection against disseminated disease in infants but has little effect on prevention of adult pulmonary disease. Newer parenteral immunization prime boost regimes may provide improved protection in experimental animal models but are unproven in man so that there remains a need for new and improved immunization strategies. Mice were immunized parenterally, intranasally or simultaneously by both routes with BCG or recombinant mycobacterial antigens plus appropriate adjuvants. They were challenged with Mycobacterium tuberculosis (Mtb) and the kinetics of Mtb growth in the lungs measured. We show that simultaneous immunization (SIM) of mice by the intranasal and parenteral routes is highly effective in increasing protection over parenteral BCG administration alone. Intranasal immunization induces local pulmonary immunity capable of inhibiting the growth of Mtb in the early phase (the first week) of infection, while parenteral immunization has a later effect on Mtb growth. Importantly, these two effects are additive and do not depend on priming and boosting the immune response. The best SIM regimes reduce lung Mtb load by up to 2 logs more than BCG given by either route alone. These data establish SIM as a novel and highly effective immunization strategy for Mtb that could be carried out at a single clinic visit. The efficacy of SIM does not depend on priming and boosting an immune response, but SIM is complementary to prime boost strategies and might be combined with them.


Quality and safety in pediatric anesthesia: how can guidelines, checklists, and initiatives improve the outcome?
Cognitive aids are tangible or intangible instruments that guide users in decision-making and in the completion of a complex series of tasks. Common examples include mnemonics, checklists, and algorithms. Cognitive aids constitute very effective approaches to achieve well tolerated, high quality healthcare because they promote highly reliable processes that reduce the likelihood of failure. This review describes recent advances in quality improvement for pediatric anesthesiology with emphasis on application of cognitive aids to impact patient safety and outcomes. Quality improvement encourages the examination of systems to create stable processes and ultimately high-value care. Quality improvement initiatives in pediatric anesthesiology have been shown to improve outcomes and the delivery of efficient and effective care at many institutions. The use of checklists, in particular, improves adherence to evidence-based care in crisis situations, decreases catheter-associated bloodstream infections, reduces blood product utilization, and improves communication during the patient handoff process. Use of this simple tool has been associated with decreased morbidity, fewer medical errors, improved provider satisfaction, and decreased mortality in nonanesthesia disciplines as well. Successful quality improvement initiatives utilize cognitive aids such as checklists and have been shown to optimize pediatric patient experience and anesthesia outcomes and reduce perioperative complications.


Motion and vision: why animals move their eyes.
Nearly all animals with good vision have a repertoire of eye movements. The majority show a pattern of stable fixations with fast saccades that shift the direction of gaze. These movements may be made by the eyes themselves, or the head, or in some insects the whole body. The main reason for keeping gaze still during fixations is the need to avoid the blur that results from the long response time of the photoreceptors. Blur begins to degrade the image at a retinal velocity of about 1 receptor acceptance angle per response time. Some insects (e.g. hoverflies) stabilise their gaze much more rigidly than this rule implies, and it is suggested that the need to see the motion of small objects against a background imposes even more stringent conditions on image motion. A third reason for preventing rotational image motion is to prevent contamination of the translational flow-field, by which a moving animal can judge its heading and the distances of objects. Some animals do let their eyes rotate smoothly, and these include some heteropod molluscs, mantis shrimps and jumping spiders, all of which have narrow linear retinae which scan across the surroundings. Hymenopteran insects also rotate during orientation flights at speeds of 100-200 degrees s-1. This is just consistent with a blur-free image, as are the scanning speeds of the animals with linear retinae.


A mechanism for detecting coincidence of auditory and visual spatial signals.
Information about the world is captured by our separate senses, and must be integrated to yield a unified representation. This raises the issue of which signals should be integrated and which should remain separate, as inappropriate integration will lead to misrepresentation and distortions. One strong cue suggesting that separate signals arise from a single source is coincidence, in space and in time. We measured increment thresholds for discriminating spatial intervals defined by pairs of simultaneously presented targets, one flash and one auditory sound, for various separations. We report a 'dipper function', in which thresholds follow a 'U-shaped' curve, with thresholds initially decreasing with spatial interval, and then increasing for larger separations. The presence of a dip in the audiovisual increment-discrimination function is evidence that the auditory and visual signals both input to a common mechanism encoding spatial separation, and a simple filter model with a sigmoidal transduction function simulated the results well. The function of an audiovisual spatial filter may be to detect coincidence, a fundamental cue guiding whether to integrate or segregate.


Yoga for warriors: An intervention for veterans with comorbid chronic pain and PTSD.
Comorbid chronic pain and posttraumatic stress disorder (PTSD) is common in veterans; this comorbidity is associated with increased severity and poorer prognosis when compared to each outcome alone. Yoga has been shown to be effective for chronic pain and promising for PTSD, but yoga for comorbid pain and PTSD has not been examined. This article offers empirical support for a yoga intervention for comorbid chronic pain and PTSD in a veteran population. Results are presented from a 4-year pilot yoga intervention for comorbid chronic pain and PTSD at a large, urban Veterans Affairs Medical Center. Based on the fear avoidance model of pain, the intervention used a cross-sectional, open-trial design with pre- and postmeasures. T test analyses were conducted on program completers (N = 49; out of 87 initially enrolled, 44% attrition rate), who were primarily African American (69%) and male (61%) and had a mean age of 51.41 years (SD = 11.32). Results indicated trend-level reductions in overall PTSD symptoms, as measured by the PTSD Checklist for DSM-5 (p = .02, d = 0.38) and in symptom cluster scores of negative alterations of cognitions and mood (p = .03, d = 0.36) and arousal and reactivity (p = .03, d = 0.35). Veterans reported significant improvement in ability to participate in social activities (p < .001, d = 0.44) and significant reductions in kinesiophobia (fear of movement or physical activity; p < .001, d = 0.85). On a satisfaction measure with a range of 1 (quite dissatisfied) to 4 (extremely satisfied), the mean rating was 3.74 (SD = 0.33). Yoga is a feasible and effective intervention for veterans with comorbid chronic pain and PTSD. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Cancer: pathological nuclear reprogramming?
The ability of stem cells to self-renew and generate different lineages during development and organogenesis is a fundamental, tightly controlled, and generally unidirectional process, whereas the 'immortality' of cancer cells could be regarded as pathological self-renewal. The molecular mechanisms that underpin the generation of induced pluripotent stem cells are remarkably similar to those that are deregulated in cancer - so much so that aberrant reprogramming is tumorigenic. The similarities also suggest that mutations in genes implicated in DNA methylation dynamics might represent a hallmark of cancers with a stem cell origin, and they highlight an alternative view of cancer that may be of clinical benefit.